Ibuprofen Llysine

Ibuprofen Lysine is indicated to close a clinically significant patent ductus arteriosus (PDA) in premature infants weighing between 500 and 1500 g, who are no more than 32 weeks gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support, etc.) is ineffective. The clinical trial was conducted among infants with an asymptomatic PDA. However, the consequences beyond 8 weeks after treatment have not been evaluated; therefore, treatment should be reserved for infants with clear evidence of a clinically significant PDA.

Ibuprofen Lysine is contraindicated in:

• Preterm infants with proven or suspected infection that is untreated;
• Preterm infants with congenital heart disease in whom patency of the PDA is necessary for satisfactory pulmonary or systemic blood flow (e.g., pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta);
• Preterm infants who are bleeding, especially those with active intracranial hemorrhage or gastrointestinal bleeding;
• Preterm infants with thrombocytopenia;
• Preterm infants with coagulation defects;
• Preterm infants with or who are suspected of having necrotizing enterocolitis;
• Preterm infants with significant impairment of renal function.

5.1 General

There are no long-term evaluations of the infants treated with ibuprofen at durations greater than the 36 weeks post-conceptual age observation period. Ibuprofen’s effects on neurodevelopmental outcome and growth as well as disease processes associated with prematurity (such as retinopathy of prematurity and chronic lung disease) have not been assessed.

5.2 Infection

Ibuprofen Lysine may alter the usual signs of infection. The physician must be continually on the alert and should use the drug with extra care in the presence of controlled infection and in infants at risk of infection.

5.3 Platelet Aggregation

Ibuprofen Lysine, like other non-steroidal anti-inflammatory agents, can inhibit platelet aggregation. Preterm infants should be observed for signs of bleeding. Ibuprofen has been shown to prolong bleeding time (but within the normal range) in normal adult subjects. This effect may be exaggerated in patients with underlying hemostatic defects (see CONTRAINDICATIONS).

5.4 Bilirubin Displacement

Ibuprofen has been shown to displace bilirubin from albumin binding-sites; therefore, it should be used with caution in patients with elevated total bilirubin.

5.5 Administration

Ibuprofen Lysine should be administered carefully to avoid extravascular injection or leakage, as solution may be irritating to tissue.

6.1 Clinical Trials Experience

The most frequently reported adverse events with Ibuprofen Lysine were as shown in Table 1.

6.2 Renal Function

Compared to placebo, there was a small decrease in urinary output in the ibuprofen group on days 2-6 of life, with a compensatory increase in urine output on day 9. In other studies, adverse events classified as renal insufficiency including oliguria, elevated BUN, elevated creatinine, or renal failure were reported in ibuprofen treated infants.

6.3 Additional Adverse Events

The adverse events reported in the multicenter study and of unknown association include tachycardia, cardiac failure, abdominal distension, gastroesophageal reflux, gastritis, ileus, inguinal hernia, injection site reactions, cholestasis, various infections, feeding problems, convulsions, jaundice, hypotension, and various laboratory abnormalities including neutropenia, thrombocytopenia, and hyperglycemia.

6.4 Post-marketing Experience

The following adverse reactions have been identified from spontaneous post-marketing reports or published literature: gastrointestinal perforation, necrotizing enterocolitis, and pulmonary hypertension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency, or establish a causal relationship to drug exposure.

The following signs and symptoms have occurred in individuals (not necessarily in premature infants) following an overdose of oral ibuprofen: breathing difficulties, coma, drowsiness, irregular heartbeat, kidney failure, low blood pressure, seizures, and vomiting. There are no specific measures to treat acute overdosage with Ibuprofen Lysine. The patient should be followed for several days because gastrointestinal ulceration and hemorrhage may occur.

17.1 General

Patients’ caregivers should be informed that the effects of ibuprofen on infants’ neurodevelopmental outcome, growth and disease process with prematurity have not been assessed in long-term studies.

17.2 Infection

Ibuprofen Lysine may alter signs of infection. Patients’ caregivers should be informed that the infant will be carefully monitored for any signs of infection.

17.3 Platelet Aggregation

Patients’ caregivers should be informed that like other NSAIDS, Ibuprofen Lysine can inhibit clot formation therefore their infant will be monitored for any signs of bleeding.

17.4 Bilirubin Displacement

Patients’ caregivers should be informed that the infants’ blood will be tested for increased levels of total bilirubin.

17.5 Administration

Patients’ caregivers should be informed that the infants’ skin and tissues will be monitored as leakage from administration may be irritating to tissue.

Manufactured by: AAIPharma Services, Charleston, SC 29405, U.S.A.

For: Prasco Laboratories, Mason, OH 45040, U.S.A.

Revised: January 2016 PC4826B